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Updated: Jun 12, 2026

Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Tob1 is a constitutively expressed repressor of liver regeneration
Karen J Ho1, Nhue L Do, Hasan H Otu
1Department of Surgery, the Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Abstract:
How proliferative and inhibitory signals integrate to control liver regeneration remains poorly understood. A screen for antiproliferative factors repressed after liver injury identified transducer of ErbB2.1 (Tob1), a member of the PC3/BTG1 family of mito-inhibitory molecules as a target for further evaluation. Tob1 protein decreases after 2/3 hepatectomy in mice secondary to posttranscriptional mechanisms. Deletion of Tob1 increases hepatocyte proliferation and accelerates restoration of liver mass after hepatectomy. Down-regulation of Tob1 is required for normal liver regeneration, and Tob1 controls hepatocyte proliferation in a dose-dependent fashion. Tob1 associates directly with both Caf1 and cyclin-dependent kinase (Cdk) 1 and modulates Cdk1 kinase activity. In addition, Tob1 has significant effects on the transcription of critical cell cycle components, including E2F target genes and genes involved in p53 signaling. We provide direct evidence that levels of an inhibitory factor control the rate of liver regeneration, and we identify Tob1 as a crucial check point molecule that modulates the expression and activity of cell cycle proteins.
Insights
Transducer of ErbB2.1 (Tob1), an inhibitory molecule, controls liver regeneration. Its down-regulation is essential for liver regrowth after injury, highlighting Tob1 as a key checkpoint.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Cycle Regulation
Background:
- Liver regeneration involves complex signaling pathways.
- Antiproliferative factors' roles in liver repair are not fully understood.
- Transducer of ErbB2.1 (Tob1) is a known mito-inhibitory molecule.
Purpose of the Study:
- To investigate the role of Tob1 in liver regeneration.
- To determine how Tob1 levels influence hepatocyte proliferation.
- To identify Tob1 as a potential checkpoint in liver repair.
Main Methods:
- Screening for antiproliferative factors after liver injury.
- Analyzing Tob1 protein levels post-hepatectomy in mice.
- Evaluating hepatocyte proliferation in Tob1-deleted mice.
- Investigating Tob1 interactions with cell cycle proteins (e.g., Cdk1).
- Assessing Tob1's impact on gene transcription (E2F, p53 signaling).
Main Results:
- Tob1 protein levels decrease after partial hepatectomy via posttranscriptional mechanisms.
- Tob1 deletion enhances hepatocyte proliferation and accelerates liver mass restoration.
- Tob1 down-regulation is necessary for normal liver regeneration.
- Tob1 directly interacts with Caf1 and Cdk1, modulating Cdk1 activity.
- Tob1 influences the transcription of key cell cycle genes.
Conclusions:
- Tob1 acts as a crucial checkpoint molecule in liver regeneration.
- Tob1 levels directly control the rate of liver regeneration.
- Modulation of Tob1 impacts hepatocyte proliferation and cell cycle protein activity.
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